Cellular Mechanisms of Photoreceptor Disk Morphogenesis

项目摘要 光感受器纤毛是所有初级纤毛中最精细的。它的质膜广泛 放大以形成包含非常高浓度的视觉感受器的盘膜堆叠， 视黄素。这堆圆盘形成光感受器外段，它的组织是视觉的中心 敏感度和空间分辨率。这项拟议研究的总体目标是了解细胞 参与盘膜形态发生的机制。 该研究计划建立在应用分子工具的基础上，使用先进的显微镜， 包括EM断层扫描和活细胞超分辨率显微镜，用于高分辨率的3D分析。这个 拟议研究的长期目标是提供对光感受器盘的分子理解 形态发生，包括将必需蛋白质输送到膜生长部位的机制。 具体目标将解决视蛋白纤毛定位的未知方面，以及视盘的作用 利用小鼠体内和小鼠杆状感光器启动板层生长的形态发生蛋白 含有未特化纤毛的细胞的培养。我们的发现将为我们提供对 感光细胞生物学。它们也将是我们理解视网膜发病机制的基础 由于盘膜形态发生的扰动而引起的疾病。

Project Summary The photoreceptor cilium is the most elaborate of all primary cilia. Its plasma membrane is extensively amplified to form a stack of disk membranes that contain a very high concentration of the visual receptor, opsin. This stack of disks forms the photoreceptor outer segment, and its organization is central to visual sensitivity and spatial resolution. The overall goal of the proposed research is to understand the cellular mechanisms involved in the morphogenesis of the disk membranes. The research plan is built on the application of molecular tools, with the use of advanced microscopy, including EM tomography and live-cell super-resolution microscopy, for high resolution, 3-D analysis. The long-term goal of the proposed research is to provide a molecular understanding of photoreceptor disk morphogenesis, including the mechanisms for delivering essential proteins to the site of membrane growth. The Specific Aims will address unknown aspects of the ciliary localization of opsin, and the roles of disk morphogenetic proteins in initiating lamellar growth, using both mouse rod photoreceptors in vivo and cultures of cells bearing unspecialized cilia. Our findings will provide understanding of a key area of photoreceptor cell biology. They will also be fundamental to our understanding of the pathogenesis of retinal disease that ensues from perturbations of disk membrane morphogenesis.